PAA, A New Dawn , FDA ODD Approval and Entering Phase II MND Trial, page-969

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Icebluedenim

366 Posts.

615

03/08/24

07:50

Post #: 75053914
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Originally posted by Quiltman: ↑

Of interest, new detailed study on TDP-43 accumulation and the role of autophagy :

Ageing Res Rev. 2024 Jul 27:100:102441. doi: 10.1016/j.arr.2024.102441.

TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: From pathomechanisms to therapeutic strategies

"Accumulation of TDP-43 aggregates in the central nervous system is a hallmark of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Autophagy, a major and highly conserved degradation pathway, holds the potential for degrading aggregated TDP-43 and alleviating FTLD/ALS".

"Crucially, the harmful impacts of misfolded, unfolded, or aggregated TDP-43 can be mitigated by enhancing or restoring protein quality control mechanisms. Thus, comprehending how these clearance pathways facilitate the breakdown of misfolded, unfolded, or aggregated TDP-43, and potentially manipulating them, could be beneficial for enhancing neuronal viability and mitigating neurodegeneration."

" Despite increased interest in autophagy activation as a potential therapeutic strategy for promoting clearance of protein aggregates and neuropotection, treatments targeting autophagy should be carefully evaluated as overactivation of autophagy accelerates the progression of neurodegenerative diseases. In addition, the development or establishment of a drug delivery system across the blood-brain barrier that targets the central nervous system may allow lower effective drug doses for treatment. Future studies should focus on developing therapeutic interventions that precisely restore the function of protein clearance systems in FTLD and ALS."

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That is a very comprehensive review and summary of TDP-43 proteinopathy that highlights the importance of the mechanisms of autophagy and its rising prominence for therapeutic outcomes across a number of neuro diseases. Great find!! I'm sure MT will be across it, but doubly sure Nicky is living and breathing that stuff for breakfast. I'm thinking a PAA science thread would work to maintain decent continuity of science news and commentary, (and reduce fluff contamination from other SH interest topics), and there happens to be a nice little science update to kick it off...
cheers,
Ice

PAA Price at posting: 19.5¢ Sentiment: Buy Disclosure: Held
18 Upvote

0 Great analysis

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